Gender Difference in Immune Defense Mechanisms: Potential Application to the Management of Combat Associated Major Trauma

摘要

Nuclear factor-kappaB (NF-KB) plays an important role in regulating the expression of a variety of rapid response genes involved in the coordinated response to inflammation, injury and sepsis. The inducible nitric oxide synthase (iNOS) is primarily regulated by transcriptional mechanisms and activation of NE-KB by pro-inflammatory mediators (e.g. LPS) plays a pivotal role in the process. We have investigated NF- KB activation by LPS in Kupffer cells of LPS tolerant and non- tolerant male and female rats. In addition we have studied the modulation of hepatic nitric oxide production by LPS tolerance and ethanol, and the gender dependence of redox balance (as assessed by GSH and GSSG assay) in Kupffer cells of LPS tolerant rats. Finally we have also studied sexual dimorphism of gene expression pursuant to NF-KB activation, in cross-tolerance between acute ethanol and LPS. Gender dependent modulation of iNOS mRNA and COX- 2 mRNA expression by LPS and ethanol was shown in liver cells.